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• W4382806754 abstract "Gastric cancer is the fifth most common cancer worldwide and even though its incidence has decreased in the Western world, it is still the fourth most common cause of cancer-related death. The reason for poor prognosis relates mainly to late diagnosis and lack of effective treatments for metastasized disease. Molecular subtyping was performed according to two classifications: A) The Cancer Genome Atlas (TCGA) classification into 1) Epstein–Barr virus (EBV) positive, 2) Microsatellite instability (MSI), 3) Chromosomal instability (CIN) which is characterized by intestinal histology, and 4) Genetically stable (GS) which was defined by diffuse histology. B) Asian Cancer Research Group (ACRG) classification into 1) MSI, 2) Epithelial–mesenchymal transition (EMT) defined using E-cadherin staining, 3) p53 positive, and 4) p53 negative. We aim to find a set of immunohistochemical marker proteins with which we could do reliable subtyping from histological samples. This could reveal a novel way of classifying gastric cancer which is easier to implement into clinical decision making compared to genome sequencing methods. We examined a cohort of 283 gastric cancer patients operated on at Helsinki University Hospital between 2000 and 2009. Clinical data were collected from patient records and information on time and cause of death from the Digital and Population Data Services Agency. We have constructed a tumor tissue microarray (TMA) which was stained for the following immunohistochemical markers: MSI markers MSH2, MSH6, MLH1, and PMS2, p53, E-cadherin, and EBV in situ hybridization EBERISH. According to the TCGA classification, we found 35 patients (15.7%) of the EBV+ subtype, 38 (17.0%) with MSI+, 63 (28.3%) with CIN or with an intestinal histology according to the Laurén classification, and 87 (39.0%) with GS or diffuse histology. Using the ACRG classification, we found 41 patients (20.0%) with MSI+, 44 (21,5%) with EMT+, 41 (20,0%) with p53+ and 79 (38,5%) with p53–. In univariate analysis, EBV subtype had the worst prognosis with a HR of 1.87 (95% CI 1.06–3.29, p=0.031) compared to the most benign subtype CIN. Multivariate analysis showed that by the ACRG classification p53+ had the best prognosis whereas MSI, p53–, and EMT had poorer prognosis with HR 1.56 (95% CI 0.88–2.78, p=0.131), HR 1.93 (95% CI 1.02–3.64, p=0.044), and HR 2.31 (95% CI 1.17–4.57, p=0.016), respectively. EBERISH, MSI, p53, and the Laurén classification are not statistically significant biomarkers individually, but in a molecular subtype model they proved to be an effective tool. Immunohistochemical analysis can be used to identify molecular subtypes of gastric cancer. The method is inexpensive and fast yet reveals significant information for clinical decision making. Determination of the molecular subtype from a histological sample could help in better aiming treatments for appropriate patient subgroups and could provide valuable information on the prognosis." @default.
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• W4382806754 date "2023-06-01" @default.
• W4382806754 modified "2023-09-23" @default.
• W4382806754 title "PD-1 Prognostic effect of immunohistochemically classified molecular subtypes in gastric cancer" @default.
• W4382806754 doi "https://doi.org/10.1016/j.annonc.2023.04.028" @default.
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